Chronic rhinosinusitis affects about 15% of the adult population in the United States. It is likely that a variety of abnormalities give rise to this disorder. Chronic rhinosinusitis is an almost invariable feature of the autosomal recessive disorder Cystic Fibrosis (CF), which is caused by mutations in the CFTR gene. We have been exploring the possibility that patients with rhinosinusitis have a higher rate of defects in the CFTR gene than the normal population. Studies performed during the prior grant period identified an increased frequency of carriers of CF mutations among patients with chronic rhinosinusitis (n=11). Excessive genetic analysis and studies that evaluated CFTR function in vivo (sweat chloride test and nasal potential difference measurement) has been complemented on none patients, and none have evidence of CF. These data suggest that CFTR plays an etiologic role in chronic rhinosinusitis in the absence of cystic fibrosis. The overall goal of the current proposal is to explore the relationship between CFTR and chronic rhinosinusitis by pursuing the following aims: 1. To establish the prevalence of CF carriers among patients with chronic rhinosinusitis by genetically screening at least 100 additional rhinosinusitis patients and an additional 120 controls enrolled by the Clinical Core. 2. To determine whether chronic rhinosinusitis patients with a CF mutation have clinical and/or biochemical features that distinguish them from patients without CF mutations. 3. To determine whether family members that have inherited a CF mutation have a higher frequency of chronic rhinosinusitis than those that have not inherited a CF mutation. 4. To determine whether the prevalence of chronic rhinosinusitis in obligate carriers of CF mutations (i.e. parents of Cystic Fibrosis patients) is higher than in the general population. Use of complementary approaches and sufficiently large populations should minimize the chance of erroneously accepting or rejecting the hypothesis that chronic rhinosinusitis patients have an increased frequency of CF mutations. This is critical since the potential health impact of this hypothesis could be substantial, and if correct, may enable the identification of patients who could benefit from therapies that are not currently employed in the treatment of rhinosinusitis.